Expression and pharmacological modulation of visceral pain-induced conditioned place aversion in mice

Pain encompasses both a sensory as well as an affective dimension and these are differentially processed in the brain and periphery. It is therefore important to develop animal models to reflect the non-reflexive assays in pain. In this study, we compared effects of the mu opioid receptor agonist morphine, the nonsteroidal anti-inflammatory drug ketoprofen and the kappa receptor opioid agonist U50,488H and antagonist JDTic on acetic acid-induced stretching and acetic acid-induced aversion in the condition place aversion (CPA) test in male ICR mice. Intraperitoneal administration of acetic acid (0.32-1%) was equipotent in stimulating stretching and CPA. Ketoprofen, morphine and U50,488H all inhibited the acid-induced stretching. Ketoprofen and morphine also blocked the acid-induced CPA but U50,488H failed to do so. The reversal ability of ketoprofen and morphine on acid-induced CPA is unique to pain-stimulated place aversion since these drugs failed to reduce non-noxious LiCl-induced CPA. Overall, this study characterized and validated a preclinical mouse model of pain-related aversive behavior that can be used to assess genetic and biological mechanisms of pain as well as improving the predictive validity of preclinical studies on candidate analgesics.